tailieunhanh - Báo cáo khoa học:Insulin-like growth factor 1 signaling regulates cytosolic sialidase Neu2 expression during myoblast differentiation and hypertrophy

Cytosolic sialidase (neuraminidase 2; Neu2) is an enzyme whose expression increases during myoblast differentiation. Here we show that insulin-like growth factor 1 (IGF1)-induced hypertrophy of myoblasts notably increa-ses Neu2 synthesis by activation of the phosphatidylinositol 3-kinase/AKT/ mammalian target of rapamycin (P13K/AKT/mTOR) pathway, whereas the proliferative effect mediated by activation of the extracellular regulated kinase 1⁄2 (ERK1⁄2) pathway negatively contributed to Neu2 activity | ỊFEBS Journal Insulin-like growth factor 1 signaling regulates cytosolic sialidase Neu2 expression during myoblast differentiation and hypertrophy Alessandro Fanzani Francesca Colombo Roberta Giuliani Augusto Preti and Sergio Marchesini Department of BiomedicalSciences and Biotechnology Unit of Biochemistry University of Brescia Italy Keywords AKT IGF-1 myoblast Neu2 sialidase gangliosides Correspondence A. Fanzani University of Brescia Department of Biomedical Sciences and Biotechnology viale Europa 11 25123 Brescia Italy Fax 39 030 3701157 Tel 39 030 3717568 E-mail fanzani@ Received 5 May 2006 revised 12 June 2006 accepted 13 June 2006 doi Cytosolic sialidase neuraminidase 2 Neu2 is an enzyme whose expression increases during myoblast differentiation. Here we show that insulin-like growth factor 1 IGF1 -induced hypertrophy of myoblasts notably increases Neu2 synthesis by activation of the phosphatidylinositol 3-kinase AKT mammalian target of rapamycin P13K AKT mTOR pathway whereas the proliferative effect mediated by activation of the extracellular regulated kinase 1 2 ERK1 2 pathway negatively contributed to Neu2 activity. Accordingly the differentiation L6MLC IGF-1 cell line in which the forced postmitotic expression of insulin-like growth factor 1 stimulates a dramatic hypertrophy was accompanied by a stronger Neu2 increase. Indeed the hypertrophy induced by transfection of a constitutively activated form of AKT was able to induce high Neu2 activity in C2C12 cells whereas the transfection of a kinase-inactive form of AKT prevented myotube formation triggering Neu2 downregulation. Neu2 expression was strictly correlated with IGF-1 signaling also in C2 myoblasts overexpressing the insulin-like growth factor 1 binding protein 5 and therefore not responding to endogenously produced insulin-like growth factor 1. Although Neu2-transfected myoblasts exhibited stronger differentiation we demonstrated that Neu2 .